Department of Basic Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Front Endocrinol (Lausanne). 2023 Feb 17;14:1089527. doi: 10.3389/fendo.2023.1089527. eCollection 2023.
SET domain-containing 5 (SETD5) is an uncharacterized member of the protein lysine methyltransferase family and is best known for its transcription machinery by methylating histone H3 on lysine 36 (H3K36). These well-characterized functions of SETD5 are transcription regulation, euchromatin formation, and RNA elongation and splicing. SETD5 is frequently mutated and hyperactive in both human neurodevelopmental disorders and cancer, and could be down-regulated by degradation through the ubiquitin-proteasome pathway, but the biochemical mechanisms underlying such dysregulation are rarely understood. Herein, we provide an update on the particularities of SETD5 enzymatic activity and substrate specificity concerning its biological importance, as well as its molecular and cellular impact on normal physiology and disease, with potential therapeutic options.
SET 结构域包含蛋白 5（SETD5）是蛋白赖氨酸甲基转移酶家族中一个尚未明确功能的成员，其最广为人知的功能是通过将组蛋白 H3 赖氨酸 36（H3K36）甲基化来参与转录机制。SETD5 的这些功能已被充分研究，包括转录调控、常染色质形成、RNA 延伸和剪接。SETD5 在人类神经发育障碍和癌症中经常发生突变和过度活跃，并且可以通过泛素-蛋白酶体途径降解进行下调，但这种失调的生化机制很少被理解。在此，我们提供了关于 SETD5 酶活性和底物特异性的最新信息，这些信息涉及到其生物学重要性，以及其对正常生理和疾病的分子和细胞影响，同时也讨论了潜在的治疗选择。
